Systematic Review on the Effectiveness of Strategies for Increasing Insulin Bioavailability in Oral Route Delivery Systems Based on Manufacturing Techniques and Materials Used
Abstract
Diabetes is a metabolic disease characterized by hyperglycemia due to impaired insulin secretion, insulin action, or both. All patients with type 1 diabetes and many type 2 diabetes require insulin therapy to achieve reasonable glycemic control. During this time, insulin is given through the subcutaneous injection route because it can be destroyed by gastric acid when given orally. Until now, many studies have developed oral insulin therapy using various delivery system strategies. This systematic literature review aims to answer several questions about the effect of technique and material on increasing oral insulin bioavailability and the best technique and type of material that can produce the best oral insulin bioavailability. We searched for published articles regarding the development of oral route insulin. Bioavailability parameters were assessed based on plasma insulin levels for relative bioavailability values and/or plasma glucose levels for pharmacological bioavailability values. Conclusion: The manufacturing technique in the delivery system affects insulin stability in maintaining its conformation to provide a therapeutic effect. The type of substance affects insulin bioavailability through its properties in paving the way for insulin across various barriers in the digestive tract. To date, the best results in the development of oral insulin have obtained oral insulin bioavailability of 73.10% achieved by mesoporous silica nanoparticles (MSN) delivery system with layer-by-layer technique coated with [poly (methacrylic acid-co-vinyl triethoxylsilane)] (PMV)].
Keywords: bioavailability, diabetes, insulin, nanoparticles, oral delivery system.
Keywords:
bioavailability, diabetes, insulin, nanoparticles, oral delivery systemDOI
https://doi.org/10.22270/jddt.v11i6.5132References
WHO; Diabetes, 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes
Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. "Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition". Diabetes Res Clin Pract, 2019; 157:107843. https://doi.org/10.1016/j.diabres.2019.107843
(a). Kementerian Kesehatan RI. CEGAH, CEGAH, DAN CEGAH: SUARA DUNIA PERANGI DIABETES. Indonesia; 2018. Available at: https://www.kemkes.go.id/article/print/18121200001/cegah-cegah-dan-cegah-suara-dunia-perangi-diabetes.html. Accessed February 8, 2021.
Shah RB, Patel M, Maahs DM, Shah VN, "Insulin delivery methods: Past, present and future" Int J Pharm Investig, 2016; 6(1):1–9. Available from: https://pubmed.ncbi.nlm.nih.gov/27014614 https://doi.org/10.4103/2230-973X.176456
Freeland B, Farber MS. "A Review of Insulin for the Treatment of Diabetes Mellitus" Home Healthc now, 2016 Sep; 34(8):416–23. https://doi.org/10.1097/NHH.0000000000000446
Wong CY, Martinez J, Dass CR, "Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities" J Pharm Pharmacol, 2016 Sep; 68(9):1093–108. Available from: https://doi.org/10.1111/jphp.12607
Krishnaiah Y. "Pharmaceutical Technologies for Enhancing Oral Bioavailability of Poorly Soluble Drugs" J Bioequiv Availab, 2010 Jan; 1(2). https://doi.org/10.4172/jbb.1000027
Bhosle VK, Altit G, Autmizguine J, Chemtob S, "18 - Basic Pharmacologic Principles. In: Polin RA, Abman SH, Rowitch DH, Benitz WE, Fox WWBT-F and NP (Fifth E, editors" Elsevier, 2017; 187-201. DOI: https://www.sciencedirect.com/science/article/pii/B9780323352147000184
Savjani KT, Gajjar AK, Savjani JK, "Drug Solubility: Importance and Enhancement Techniques" Aktay G, Du Y-Z, Torrado J, editors, ISRN Pharm [Internet], 2012; 2012:195727. DOI: https://doi.org/10.5402/2012/195727
Fonte P, Araújo F, Reis S, Sarmento B, "Oral insulin delivery: How far are we?" J Diabetes Sci Technol, 2013; 7(2):520–31. https://doi.org/10.1177/193229681300700228
Singh AP, Guo Y, Singh A, Xie W, Jiang P, "Developments in encapsulation of insulin: Is oral delivery now possible?" J Pharm Biopharm Res, 2019; 1(2):74–93. https://doi.org/10.25082/JPBR.2019.02.005
Wong CY, Al-Salami H, Dass CR, "Fabrication techniques for the preparation of orally administered insulin nanoparticles" J Drug Target, 2021 Apr 21; 29(4):365–86. DOI: https://doi.org/10.1080/1061186X.2020.1817042
Rowley J, Slack F, "Conducting a literature review" Manag Res News, 2004; 27(6):31–9. https://doi.org/10.1108/01409170410784185
Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C, "The PRISMA 2020 statement: an updated guideline for reporting systematic reviews" BMJ, 2021; 372(71). https://doi.org/10.1136/bmj.n71
Han X, Lu Y, Xie J, Zhang E, Zhu H, Du H, et al, "Zwitterionic micelles efficiently deliver oral insulin without opening tight junctions" Nat Nanotechnol, 2020; 15(7):605–14. DOI: http://dx.doi.org/10.1038/s41565-020-0693-6
Jaafar MHM, Hamid KA, "Chitosan-Coated Alginate Nanoparticles Enhanced Absorption Profile of Insulin Via Oral Administration" Curr Drug Deliv, 2019; 16(7):672–86. https://doi.org/10.2174/1567201816666190620110748
Iqbal M, Zafar N, Fessi H, Elaissari A, "Double emulsion solvent evaporation techniques used for drug encapsulation" Int J Pharm, 2015 Dec; 496(2):173–90. https://doi.org/10.1016/j.ijpharm.2015.10.057
Chen T, Li S, Zhu W, Liang Z, Zeng Q, "Self-assembly pH-sensitive chitosan/alginate coated polyelectrolyte complexes for oral delivery of insulin" J Microencapsul [Internet], 2019; 36(1):96–107. DOI: https://doi.org/10.1080/02652048.2019.1604846
Liu L, Zhou C, Xia X, Liu Y, "Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: Preparation and functional evaluation" Int J Nanomedicine, 2016; 11:761–9. https://doi.org/10.2147/IJN.S96146
Guha A, Biswas N, Bhattacharjee K, Sahoo N, Kuotsu K, "pH responsive cylindrical MSN for oral delivery of insulin-design, fabrication and evaluation" Drug Deliv, 2016; 23(9):3552–61. https://doi.org/10.1016/j.biomaterials.2017.03.028
He Z, Santos JL, Tian H, Huang H, Hu Y, Liu L, et al, "Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin" Biomaterials, 2017; 130:28–41. DOI: http://dx.doi.org/10.1016/j.biomaterials.2017.03.028
Malathi S, Nandhakumar P, Pandiyan V, Webster TJ, Balasubramanian S, "Novel PLGA-based nanoparticles for the oral delivery of insulin" Int J Nanomedicine, 2015; 10:2207–18. https://doi.org/10.2147/IJN.S67947
Wu S, Bin W, Tu B, Li X, Wang W, Liao S, et al, "A Delivery System for Oral Administration of Proteins/Peptides Through Bile Acid Transport Channels" J Pharm Sci, 2019; 108(6):2143–52. DOI: https://doi.org/10.1016/j.xphs.2019.01.027
Liu M, Zhang J, Zhu X, Shan W, Li L, Zhong J, et al, "Efficient mucus permeation and tight junction opening by dissociable “mucus-inert” agent coated trimethyl chitosan nanoparticles for oral insulin delivery" J Control Release, 2016; 222:67–77. DOI: http://dx.doi.org/10.1016/j.jconrel.2015.12.008
Wu L, Liu M, Shan W, Zhu X, Li L, Zhang Z, et al, "Bioinspired butyrate-functionalized nanovehicles for targeted oral delivery of biomacromolecular drugs" J Control Release, 2017; 262(July):273–83. DOI: http://dx.doi.org/10.1016/j.jconrel.2017.07.045
Alsulays BB, Anwer MK, Soliman GA, Alshehri SM, Khafagy ES, "Impact of penetratin stereochemistry on the oral bioavailability of insulin-loaded solid lipid nanoparticles" Int J Nanomedicine, 2019; 14:9127–38. https://doi.org/10.2147/IJN.S225086
Wang A, Yang T, Fan W, Yang Y, Zhu Q, Guo S, et al, "Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers" Adv Healthc Mater, 2019; 8(12):1–11. https://doi.org/10.1002/adhm.201801123
Ji N, Hong Y, Gu Z, Cheng L, Li Z, Li C, "Chitosan coating of zein-carboxymethylated short-chain amylose nanocomposites improves oral bioavailability of insulin in vitro and in vivo" J Control Release, 2019; 313(July):1–13. https://doi.org/10.1016/j.jconrel.2019.10.006
Agrawal AK, Urimi D, Harde H, Kushwah V, Jain S, "Folate appended chitosan nanoparticles augment the stability, bioavailability and efficacy of insulin in diabetic rats following oral administration" RSC Adv, 2015; 5(127):105179–93. https://doi.org/10.1039/C5RA19115G
Fan W, Xia D, Zhu Q, Li X, He S, Zhu C, et al, "Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery" Biomaterials, 2018; 151:13–23. DOI: https://doi.org/10.1016/j.biomaterials.2017.10.022
Jafary Omid N, Bahari Javan N, Dehpour AR, Partoazar A, Rafiee Tehrani M, Dorkoosh F, "In-vitro and in-vivo cytotoxicity and efficacy evaluation of novel glycyl-glycine and alanyl-alanine conjugates of chitosan and trimethyl chitosan nano-particles as carriers for oral insulin delivery" Int J Pharm, 2018; 535(1–2):293–307. https://doi.org/10.1016/j.ijpharm.2017.11.020
Zhang L, Zhang YX, Qiu JN, Li J, Chen W, Guan YQ, "Preparation and Characterization of Hypoglycemic Nanoparticles for Oral Insulin Delivery" Biomacromolecules, 2017; 18(12):4281–91. https://doi.org/10.1021/acs.biomac.7b01322
Mumuni MA, Kenechukwu FC, Ofokansi KC, Attama AA, Díaz DD, "Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment" Carbohydr Polym, 2020; 229(June 2019):115506. DOI: https://doi.org/10.1016/j.carbpol.2019.115506
Ukai H, Iwasa K, Deguchi T, Morishita M, Katsumi H, Yamamoto A, "Enhanced intestinal absorption of insulin by capryol 90, a novel absorption enhancer in rats: Implications in oral insulin delivery" Pharmaceutics, 2020; 12(5):1–16. https://doi.org/10.3390/pharmaceutics12050462
Fang Y, Wang Q, Lin X, Jin X, Yang D, Gao S, et al, "Gastrointestinal Responsive Polymeric Nanoparticles for Oral Delivery of Insulin: Optimized Preparation, Characterization, and In Vivo Evaluation" J Pharm Sci, 2019; 108(9):2994–3002. DOI: https://doi.org/10.1016/j.xphs.2019.04.020
Zhang P, Xu Y, Zhu X, Huang Y, "Goblet cell targeting nanoparticle containing drug-loaded micelle cores for oral delivery of insulin" Int J Pharm, 2015; 496(2):993–1005. https://doi.org/10.1016/j.ijpharm.2015.10.078
Sun L, Liu Z, Tian H, Le Z, Liu L, Leong KW, et al, "Scalable Manufacturing of Enteric Encapsulation Systems for Site-Specific Oral Insulin Delivery" Biomacromolecules, 2019; 20(1):528–38. https://doi.org/10.1021/acs.biomac.8b01530
Li L, Jiang G, Yu W, Liu D, Chen H, Liu Y, et al, "Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin" Mater Sci Eng C, 2017; 70(Part 2):278–86. DOI: http://dx.doi.org/10.1016/j.msec.2016.08.083
Liu C, Shan W, Liu M, Zhu X, Xu J, Xu Y, et al, "A novel ligand conjugated nanoparticles for oral insulin delivery" Drug Deliv, 2016; 23(6):2015–25. https://doi.org/10.3109/10717544.2015.1058433
Sahoo P, Leong KH, Nyamathulla S, Onuki Y, Takayama K, Chung LY, "Chitosan complexed carboxymethylated iota-carrageenan oral insulin particles: Stability, permeability and in vivo evaluation" Mater Today Commun, 2019; 20(June):100557. DOI: https://doi.org/10.1016/j.mtcomm.2019.100557
Sheng J, He H, Han L, Qin J, Chen S, Ru G, et al, "Enhancing insulin oral absorption by using mucoadhesive nanoparticles loaded with LMWP-linked insulin conjugates" J Control Release, 2016; 233:181–90. https://doi.org/10.1016/j.jconrel.2016.05.015
Sun S, Liang N, Yamamoto H, Kawashima Y, Cui F, Yan P, "pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin" Int J Nanomedicine, 2015; 10:3489–98. https://doi.org/10.2147/IJN.S81715
Bravo-Alfaro DA, Muñoz-Correa MOF, Santos-Luna D, Toro-Vazquez JF, Cano-Sarmiento C, García-Varela R, et al, "Encapsulation of an insulin-modified phosphatidylcholine complex in a self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin delivery" J Drug Deliv Sci Technol, 2020; 57(January):101622. DOI: https://doi.org/10.1016/j.jddst.2020.101622
Sheng J, Han L, Qin J, Ru G, Li R, Wu L, et al, "N -Trimethyl Chitosan Chloride-Coated PLGA Nanoparticles Overcoming Multiple Barriers to Oral Insulin Absorption" ACS Appl Mater Interfaces, 2015; 7(28):15430–41. https://doi.org/10.1021/acsami.5b03555
Wang X, Cheng D, Liu L, Li X, "Development of poly(hydroxyethyl methacrylate) nanogel for effective oral insulin delivery" Pharm Dev Technol, 2018; 23(4):351–7. DOI: https://doi.org/10.1080/10837450.2017.1295064
Wu J, Zheng Y, Liu M, Shan W, Zhang Z, Huang Y, "Biomimetic Viruslike and Charge Reversible Nanoparticles to Sequentially Overcome Mucus and Epithelial Barriers for Oral Insulin Delivery" ACS Appl Mater Interfaces, 2018; 10(12):9916–28. https://doi.org/10.1021/acsami.7b16524
Yazdi JR, Tafaghodi M, Sadri K, Mashreghi M, Nikpoor AR, Nikoofal-Sahlabadi S, et al, “Folate targeted PEGylated liposomes for the oral delivery of insulin: In vitro and in vivo studies” Colloids Surfaces B Biointerfaces, 2020; 194:111203. DOI: https://doi.org/10.1016/j.colsurfb.2020.111203
Hu X Bin, Tang TT, Li YJ, Wu JY, Wang JM, Liu XY, et al, “Phospholipid complex based nanoemulsion system for oral insulin delivery: Preparation, in vitro, and in vivo evaluations” Int J Nanomedicine, 2019; 14:3055–67. https://doi.org/10.2147/IJN.S198108
Liu C, Kou Y, Zhang X, Dong W, Cheng H, Mao S, “Enhanced oral insulin delivery via surface hydrophilic modification of chitosan copolymer based self-assembly polyelectrolyte nanocomplex” Int J Pharm, 2019; 554:36–47. DOI: https://doi.org/10.1016/j.ijpharm.2018.10.068
Liu J, Werner U, Funke M, Besenius M, Saaby L, Fanø M, et al, “SEDDS for intestinal absorption of insulin: Application of Caco-2 and Caco-2/HT29 co-culture monolayers and intra-jejunal instillation in rats” Int J Pharm, 2019; 560:377–84. DOI: https://doi.org/10.1016/j.ijpharm.2019.02.014
Boushra M, Tous S, Fetih G, Xue HY, Wong HL, “Development of bi-polymer lipid hybrid nanocarrier (BLN) to improve the entrapment and stability of insulin for efficient oral delivery” J Drug Deliv Sci Technol, 2019; 49:632–41. DOI: https://doi.org/10.1016/j.jddst.2019.01.007
Shan W, Zhu X, Tao W, Cui Y, Liu M, Wu L, et al, “Enhanced Oral Delivery of Protein Drugs Using Zwitterion-Functionalized Nanoparticles to Overcome both the Diffusion and Absorption Barriers” ACS Appl Mater Interfaces, 2016; 8(38):25444–53.
Ji N, Hong Y, Gu Z, Cheng L, Li Z, Li C, “Binary and Tertiary Complex Based on Short-Chain Glucan and Proanthocyanidins for Oral Insulin Delivery” J Agric Food Chem, 2017; 65(40):8866–74. https://doi.org/10.1021/acs.jafc.7b03465
Xie S, Gong YC, Xiong XY, Li ZL, Luo YY, Li YP, “Targeted folate-conjugated pluronic for the oral delivery of insulin” 2018.
Tian H, He Z, Sun C, Yang C, Zhao P, Liu L, et al, “Uniform Core–Shell Nanoparticles with Thiolated Hyaluronic Acid Coating to Enhance Oral Delivery of Insulin” Adv Healthc Mater, 2018; 7(17):1–12. https://doi.org/10.1002/adhm.201800285
Guo F, Zhang M, Gao Y, Zhu S, Chen S, Liu W, et al, “Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation” Drug Deliv, 2016; 23(6):2003–14. https://doi.org/10.3109/10717544.2015.1048489
Zhang Y, Xiong GM, Ali Y, Boehm BO, Huang YY, Venkatraman S, “Layer-by-layer coated nanoliposomes for oral delivery of insulin” Nanoscale, 2021; 13(2):776–89. https://doi.org/10.1039/D0NR06104B
Alibolandi M, Alabdollah F, Sadeghi F, Mohammadi M, Abnous K, Ramezani M, et al, “Dextran-b-poly (lactide-co-glycolide) polymersome for oral delivery of insulin: In vitro and in vivo evaluation” J Control Release, 2016; 227:58–70. DOI: http://dx.doi.org/10.1016/j.jconrel.2016.02.031
Kim KS, Kwag DS, Hwang HS, Lee ES, Bae YH, “Immense Insulin Intestinal Uptake and Lymphatic Transport using Bile Acid Conjugated Partially Uncapped Liposome” Mol Pharm, 2018; 176(1):139–48.
Zhang L, Qin H, Li J, Qiu JN, Huang JM, Li MC, et al, “Preparation and characterization of layer-by-layer hypoglycemic nanoparticles with pH-sensitivity for oral insulin delivery” J Mater Chem B, 2018; 6(45):7451–61. https://doi.org/10.1039/C8TB02113A
Verma A, Sharma S, Gupta PK, Singh A, Teja BV, Dwivedi P, et al, “Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin” Acta Biomater, 2016; 31:288–300. DOI: http://dx.doi.org/10.1016/j.actbio.2015.12.017
Fukuoka Y, Khafagy ES, Goto T, Kamei N, Takayama K, Peppas NA, et al, “Combination strategy with complexation hydrogels and cell-penetrating peptides for oral delivery of insulin” Biol Pharm Bull, 2018; 41(5):811–4. https://doi.org/10.1248/bpb.b17-00951
Yan C, Gu J, Lv Y, Shi W, Huang Z, Liao Y, “5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes” AAPS PharmSciTech, 2019; 20(1):1–8. https://doi.org/10.1208/s12249-018-1242-6
Wang J, Kong M, Zhou Z, Yan D, Yu X, Cheng X, et al, “Mechanism of surface charge triggered intestinal epithelial tight junction opening upon chitosan nanoparticles for insulin oral delivery” Carbohydr Polym, 2017;157:596–602. DOI: http://dx.doi.org/10.1016/j.carbpol.2016.10.021
Chen X, Ren Y, Feng Y, Xu X, Tan H, Li J, “Cp1-11 peptide/insulin complex loaded pH-responsive nanoparticles with enhanced oral bioactivity” Int J Pharm, 2019; 562:23–30. DOI: https://doi.org/10.1016/j.ijpharm.2019.03.020
Bahman F, Taurin S, Altayeb D, Taha S, Bakhiet M, Greish K, “Oral insulin delivery using poly (Styrene co-Maleic acid) micelles in a diabetic mouse model” Pharmaceutics, 2020; 12(11):1–17. https://doi.org/10.3390/pharmaceutics12111026
Shrestha N, Araújo F, Shahbazi MA, Mäkilä E, Gomes MJ, Herranz-Blanco B, et al, “Thiolation and Cell-Penetrating Peptide Surface Functionalization of Porous Silicon Nanoparticles for Oral Delivery of Insulin” Adv Funct Mater, 2016; 26(20):3405–16. https://doi.org/10.1002/adfm.201505252
Zhou X, Wu H, Long R, Wang S, Huang H, Xia Y, et al, “Oral delivery of insulin with intelligent glucose-responsive switch for blood glucose regulation” J Nanobiotechnology, 2020; 18(1):1–16. DOI: https://doi.org/10.1186/s12951-020-00652-z
Winarti L, Suwaldi, Martien R, Hakim L, “Formulation of insulin self nanoemulsifying drug delivery system and its in vitro-in vivo study” Indones J Pharm, 2018; 29(3):157–66. https://doi.org/10.14499/indonesianjpharm29iss3pp157
Sun S, Liang N, Gong X, An W, Kawashima Y, Cui F, et al, “Multifunctional composite microcapsules for oral delivery of insulin” Int J Mol Sci, 2017; 18(1). https://doi.org/10.3390/ijms18010054
Zhang Y, Xiong M, Ni X, Wang J, Rong H, Su Y, et al, “Virus-Mimicking Mesoporous Silica Nanoparticles with an Electrically Neutral and Hydrophilic Surface to Improve the Oral Absorption of Insulin by Breaking through Dual Barriers of the Mucus Layer and the Intestinal Epithelium” ACS Appl Mater Interfaces, 2021; 13(15):18077–88. https://doi.org/10.1021/acsami.1c00580
Zeng Z, Dong C, Zhao P, Liu Z, Liu L, Mao HQ, et al, “Scalable Production of Therapeutic Protein Nanoparticles Using Flash Nanoprecipitation” Adv Healthc Mater, 2018; 8(6):1–7. https://doi.org/10.1002/adhm.201801010
He H, Wang P, Cai C, Yang R, Tang X, “VB12-coated Gel-Core-SLN containing insulin: Another way to improve oral absorption” Int J Pharm, 2015; 493(1–2):451–9. DOI: http://dx.doi.org/10.1016/j.ijpharm.2015.08.004
Ansari MJ, Anwer MK, Jamil S, Al-Shdefat R, Ali BE, Ahmad MM, et al, “Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats” Drug Deliv, 2016; 23(6):1972–9. https://doi.org/10.3109/10717544.2015.1039666
Niu Z, Tedesco E, Benetti F, Mabondzo A, Montagner IM, Marigo I, et al, “Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers” J Control Release, 2017; 263:4–17. https://doi.org/10.1016/j.jconrel.2017.02.024
Boushra M, Tous S, Fetih G, Korzekwa K, Lebo DB, Xue HY, et al, “Development and evaluation of viscosity-enhanced nanocarrier (VEN) for oral insulin delivery” Int J Pharm, 2016; 511(1):462–72. DOI: http://dx.doi.org/10.1016/j.ijpharm.2016.07.016
Koland M, Anchan RB, Mukund SG, Sindhoor SM, “Design and investigation of alginate coated solid lipid nanoparticles for oral insulin delivery” Indian J Pharm Educ Res, 2021; 55(2):383–94. https://doi.org/10.5530/ijper.55.2.76
Deng W, Xie Q, Wang H, Ma Z, Wu B, Zhang X, “Selenium nanoparticles as versatile carriers for oral delivery of insulin: Insight into the synergic antidiabetic effect and mechanism” Nanomedicine Nanotechnology, Biol Med, 2017; 13(6):1965–74. DOI: http://dx.doi.org/10.1016/j.nano.2017.05.002
Singh S, Kushwah V, Agrawal AK, Jain S, “Insulin- and quercetin-loaded liquid crystalline nanoparticles: Implications on oral bioavailability, antidiabetic and antioxidant efficacy” Nanomedicine, 2018; 13(5):521–37. https://doi.org/10.2217/nnm-2017-0278
Heade J, McCartney F, Chenlo M, Marro OM, Severic M, Kent R, et al, “Synthesis and in vivo evaluation of insulin-loaded whey beads as an oral peptide delivery system” Pharmaceutics, 2021; 13(5):1–18. https://doi.org/10.3390/pharmaceutics13050656
Chen S, Guo F, Deng T, Zhu S, Liu W, Zhong H, et al, “Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin” AAPS PharmSciTech, 2017; 18(4):1277–87. https://doi.org/10.1208/s12249-016-0594-z
Agrawal AK, Kumar K, Swarnakar NK, Kushwah V, Jain S, “liquid Crystalline Nanoparticles”: Rationally Designed Vehicle to Improve Stability and Therapeutic Efficacy of Insulin Following Oral Administration” Mol Pharm, 2017; 14(6):1874–82. https://doi.org/10.1021/acs.molpharmaceut.6b01099
Kaur I, Nallamothu B, Kuche K, Katiyar SS, Chaudhari D, Jain S, “Exploring protein stabilized multiple emulsion with permeation enhancer for oral delivery of insulin” Int J Biol Macromol, 2021; 167:491–501. DOI: https://doi.org/10.1016/j.ijbiomac.2020.11.190
Zhu S, Chen S, Gao Y, Guo F, Li F, Xie B, et al, “Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec)” Drug Deliv, 2016; 23(6):1980–91. https://doi.org/10.3109/10717544.2015.1043472
Urimi D, Agrawal AK, Kushwah V, Jain S, “Polyglutamic Acid Functionalization of Chitosan Nanoparticles Enhances the Therapeutic Efficacy of Insulin Following Oral Administration” AAPS PharmSciTech, 2019; 20(3):1–14. https://doi.org/10.1208/s12249-019-1330-2
Wang T, Shen L, Zhang Y, Li H, Wang Y, Quan D, “Oil-soluble” reversed lipid nanoparticles for oral insulin delivery” J Nanobiotechnology, 2020; 18(1):98. https://doi.org/10.1186/s12951-020-00657-8
Xu B, Jiang G, Yu W, Liu D, Liu Y, Kong X, et al, “Preparation of poly(lactic-co-glycolic acid) and chitosan composite nanocarriers via electrostatic self assembly for oral delivery of insulin” Mater Sci Eng C, 2017;78:420–8. DOI: http://dx.doi.org/10.1016/j.msec.2017.04.113
El Leithy ES, Abdel-Bar HM, Ali RAM, “Folate-chitosan nanoparticles triggered insulin cellular uptake and improved in vivo hypoglycemic activity” Int J Pharm, 2019; 571:118708. DOI: https://doi.org/10.1016/j.ijpharm.2019.118708
Elkhatib MM, Ali AI, Al-Badrawy AS, “In vitro and in vivo comparative study of oral nanoparticles and gut iontophoresis as oral delivery systems for insulin” Biol Pharm Bull, 2021; 44(2):251–8. https://doi.org/10.1248/bpb.b20-00737
Elsayed AM, Khaled AH, Al Remawi MM, Qinna NA, Farsakh HA, Badwan AA, “Low molecular weight chitosan-insulin complexes solubilized in a mixture of self-assembled labrosol and plurol oleaque and their glucose reduction activity in rats” Mar Drugs, 2018; 16(1). https://doi.org/10.3390/md16010032
Zheng Y, Wu J, Shan W, Wu L, Zhou R, Liu M, et al, “Multifunctional Nanoparticles Enable Efficient Oral Delivery of Biomacromolecules via Improving Payload Stability and Regulating the Transcytosis Pathway” ACS Appl Mater Interfaces, 2018; 10(40):34039–49. https://doi.org/10.1021/acsami.8b13707
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